Department of Molecular Virology and Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.
Cancer Sci. 2010 Apr;101(4):843-7. doi: 10.1111/j.1349-7006.2010.01498.x. Epub 2010 Jan 18.
Membrane-type matrix metalloproteinase-1 (MT1-MMP) mediates cleavage of not only MMP-2/gelatinase A for activation, but also a variety of substrates including type I collagen (reviewed in Cancer Sci 2005; 96: 212-7). MMP-2 activation involves tissue inhibitor of MMP (TIMP)-2 as a bridging molecule between MT1-MMP and pro-MMP-2. Thus, net activity of MT1-MMP and MMP-2 is regulated in a complex manner depending on TIMP-2 concentration. During invasive growth of tumor cells in type I collagen matrix, MT1-MMP initiates denaturation of collagen into gelatin, which is subsequently digested further by MMP-2 adjacent to MT1-MMP. Coordinate action of MT1-MMP and MMP-2 may facilitate pericellular proteolysis, and enhance not only tumor invasion/migration but also cell growth. Tetraspanins as binding proteins of MT1-MMP regulate MT1-MMP subcellular localization and compartmentalization, leading to efficient MMP-2 activation and proteolysis coupled with cellular function.
膜型基质金属蛋白酶-1（MT1-MMP）不仅介导 MMP-2/明胶酶 A 的裂解以实现激活，还能切割包括 I 型胶原在内的多种底物（Cancer Sci 2005; 96: 212-7）。MMP-2 的激活涉及基质金属蛋白酶抑制剂-2（TIMP-2），作为 MT1-MMP 和 pro-MMP-2 之间的桥接分子。因此，MT1-MMP 和 MMP-2 的净活性受到 TIMP-2 浓度的影响，以复杂的方式进行调节。在 I 型胶原基质中肿瘤细胞的浸润性生长过程中，MT1-MMP 启动胶原的变性为明胶，随后 MT1-MMP 附近的 MMP-2 进一步消化明胶。MT1-MMP 和 MMP-2 的协同作用可能促进细胞周的蛋白水解，不仅增强肿瘤的侵袭/迁移，还增强细胞生长。四跨膜蛋白作为 MT1-MMP 的结合蛋白，调节 MT1-MMP 的亚细胞定位和区室化，从而有效地激活 MMP-2 并与细胞功能相关的蛋白水解。
